We propose to study in purified form a factor derived from the serum of a patient with membranoproliferative glomerulonephritis (MPGN) which is capable of activating C3 by the alternative complement pathways. The factor is a protein which can be isolated by cryoprecipitation. We have demonstarated that this factor can be isolated as a 20-24s protein which has an electrophoretic mobility in the gamma region, but is not an immunoglobulin. The factor required factor B (C3 proactivator) and Mg ions, however does not require the pesence of C1, C2, or Ca ions. This C3 activating factor is associated in cryoprecipitate with beta-1-H globulin (C3 inactivator accelerator), suggesting that it may function by interaction with this alternative pathway modulator. The proposed experiments are designed to extend our knowledge of the molecular weight of this factor and its relationship to an antigenically related normal serum alpha-2 protein. We also wish to obtain data regarding the quantity of this material in serum and cryoprecipitate from other patients with MPGN and other glomerulopathies. The C3 activating factor and beta-1-H globulin were both demonstrated in the glomerular deposits of the patient from whom the material was isolated. We wish to study other biopsy specimens in order to determine whether these factors could be involved in MPGN and other renal diseases in which complement-mediated damage is suspected. In addition we wish to study, in vitro, the effect of altering the beta-1-H globulin and C3b inactivator content of a reaction mixture upon the function of the C3 activating factor, in order to further characterize its mechanism of action.